Report: The role of macrophages in Facioscapulohumeral muscular dystrophy

Posted by Friends of FSH Research on Apr 27, 2025

Report by Dr. Nunes
See also The role of macrophages in Facioscapulohumeral muscular dystrophy

Chronic inflammation is a well-documented hallmark in FSHD patient muscles. However, the role of the immune system in FSHD is still unknown. This proposal aims to characterize macrophage hyperresponsiveness in FSHD. For this, I proposed to use the FLExDUX4 minipig with tamoxifen-inducible expression of DUX4 in skeletal muscles which recapitulates many key histological aspects of the human disease. During the second 6-month funding period, unexpected and unexplained pre-term deaths of animals preclude us from proceeding with the project in the minipig model as planned. As an alternative, we started characterizing the macrophage profile in the mouse model ACTA1 MCM; FLExD. During the current funding period, we collected mouse samples and started characterizing the macrophage profile. We also initiated the analysis of blood-isolated human monocytes which together with the characterization of the macrophage profile in the mouse model will provide an important understanding of the macrophage hyperresponsive profile in FSHD.Chronic inflammation is a well-documented hallmark in FSHD patient muscles. However, the role of the immune system in FSHD is still unknown. This proposal aims to characterize macrophage hyperresponsiveness in FSHD. For this, I proposed to use the FLExDUX4 minipig with tamoxifen-inducible expression of DUX4 in skeletal muscles which recapitulates many key histological aspects of the human disease. During the second 6-month funding period, unexpected and unexplained pre-term deaths of animals preclude us from proceeding with the project in the minipig model as planned. As an alternative, we started characterizing the macrophage profile in the mouse model ACTA1 MCM; FLExD. During the current funding period, we collected mouse samples and started characterizing the macrophage profile. We also initiated the analysis of blood-isolated human monocytes which together with the characterization of the macrophage profile in the mouse model will provide an important understanding of the macrophage hyperresponsive profile in FSHD.